The AKR mouse which has a high incidence of spontaneous thymic lymphoma, has the genetic information for the production of several endogenous retroviruses (Type C RNA viruses). They are: 1) N-ecotropic, positive with a plaque assay using rat XC cells (XC plus) and present in most tissues of the animals throughout life; 2) xenotropic virus, appearing in older animals; and 3) lymphomagenic viruses which are XC and believed to be genetic recombinants of 1 and 2. These lymphomagenic viruses are found principally in the thymus of older mice. This project proposes studies of the thymus of preleukemic animals to look at the specific changes in virus expression and cellular interaction which result in malignancy. This will be done using thymic epithelium, (primary explants and cloned established cultures), co-cultured with thymic lymphocytes. Subpopulations of these lymphocytes separated by velocity sedimentation will also be studied in these cultures. Virus expression in both epithelial cells and thymocytes will be evaluated. Tryptic peptide maps of the viral envelope protein, gp70, at the cell surface will be an additional means of distinguishing the different AKR retroviruses associated with the cells under study. These studies with thymocytes and thymic epithelial cells will be carried out in mice of different ages. Non-cultured cells will also be studied. The immune response to culured syngeneic lymphomas will be studied in both AKR and CBA mice. Specific emphasis will be placed on the relationship of antiviral immunity to prevention of lymphoma development after a challenge with viable cells.